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Query: UNIPROT:P06889 (Mol)
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Absorption and magnetic circular dichroism spectra of nonequilibrium states of hemoglobin and its derivatives formed by reduction oxidased forms of hemoproteins by thermalysed electrons at 77 degrees K were studied. Mixtures of low spin and high spin ferroforms were observed for nonequilibrium hemoglobin and its complexes with inosithexaphosphate and fluorine. The content of the high spin form increasing as follows: hemoglobin, complex with inosithexaphosphate, complex with fluorine. Only low spin forms were found for cyanide and azide complexes of hemoglobin reduced at low temperature. The spectral differences of nonequilibrium low spin ferroforms were supposed to be due to the presence of different ligands in the coordination sphere of the heme iron. The alpha-band splitting was observed for the nonequilibrium imidazole complex of hemoglobin. This effect was explained by a lowe-ring of the active centre's symmetry. The temperature relaxation of all nonequilibrium systems was investigated.
Mol Biol (Mosk)
PMID:[Absorption spectrum and magnetic circular dichroism of heme-containing proteins in nonequilibrium states. I. Hemoglobin and its derivatives]. 68 98

Absorption and magnetic curcular dichroism spectra of nonequilibrium states of peroxidase and its complexes with F-, N3-, CN- produced by reduction of oxidased forms of proteins by thermalysed electrons at 77 degrees K were studied. Mixtures of high spin and low spin ferroforms were found in nonequilibrium states of peroxidase and complexes with F- and N3-, the content of the high spin ferroform increasing as follows: N3- complex less than peroxidase less than fluorine complex. Only low spin ferroforms was found after low temperature reduction of the cyanide complex. The existence of the low spin ferroform in equilibrium states of peroxidase and its complex with F- was explained by location of iron near the porphyrine plane. In the case of azide and cyanide complexes the existence of the low spin form is due to the presence of these ligands in heme iron's coordination sphere. The temperature relaxation of all nonequilibrium forms was investigated and a possible mechanism of the process is proposed.
Mol Biol (Mosk)
PMID:[Absorption and magnetic circular dichroism spectra of nonequilibrium states of hemoproteins. III. Complexes of peroxidase]. 74 1

Absorption and magnetic circular dichroism spectra of non-equilibrium states of myoglobin and its complexes formed by reduction oxidased forms of proteins by thermalysed electrons at 77 degrees K were studied. Mixtures of high spin and low spin ferroforms were observed for nonequilibrium states of myoglobin and its complex with fluorine, the content of the high spin form is larger in the complex. Two intense peaks were found in the alpha-band region of absorption spectra of myoglobin and its spectra with F-, OH- and imidazole. This effect is due to lowering of the active centre's symmetry. Similarity of spectral characteristics of low spin ferroforms of these complexes was explained by the strong influence of distal histidine. The low temperature reduction of azide and cyanide complexes of myoglobin led to formation of nonequilibrium low spin ferroforms whose spectra demonstrate the presence of N3- and CN- in heme iron's coordination sphere. The temperature relaxation of all nonequilibrium systems were investigated.
Mol Biol (Mosk)
PMID:[Absorption and magnetic circular dichroism spectra of nonequilibrium states of hemoproteins. II. Myoglobin and its complexes]. 74

To complete assignment of the 19F nuclear magnetic resonance (NMR) spectrum of 5-fluorouracil-substituted Escherichia coli tRNA(Val), resonances from 5-fluorouracil residues involved in tertiary interactions have been identified. Because these assignments could not be made directly by the base-replacement method used to assign 5-fluorouracil residues in loop and stem regions of the tRNA, alternative assignment strategies were employed. FU54 and FU55 were identified by 19F homonuclear Overhauser experiments and were then assigned by comparison of their 19F NMR spectra with those of 5-fluorouracil-labeled yeast tRNA(Phe) mutants having FU54 replaced by adenine and FU55 replaced by cytosine. FU8 and FU12, were assigned from the 19F NMR spectrum of the tRNA(Val) mutant in which the base triple G9-C23-G12 substituted for the wild-type A9-A23-FU12. Although replacement of the conserved U8 (FU8) with A or C disrupts the tertiary structure of tRNA(Val), it has only a small effect on the catalytic turnover number of valyl-tRNA synthetase, while reducing the affinity of the tRNA for enzyme. Analysis of the 19F chemical shift assignments of all 14 resonances in the spectrum of 5-fluorouracil-substituted tRNAVal indicated a strong correlation to tRNA secondary and tertiary structure. 5-Fluorouracil residues in loop regions gave rise to peaks in the central region of the spectrum, 4.4 to 4.9 parts per million (p.p.m.) downfield from free 5-fluorouracil. However, the signal from FU59, in the T-loop of tRNA(Val), was shifted more than 1 p.p.m. downfield, to 5.9 p.p.m., presumably because of the involvement of this fluorouracil in the tertiary interactions between the T and D-loops. The 19F chemical shift moved upfield, to the 2.0 to 2.8 p.p.m. range, when fluorouracil was base-paired with adenine in helical stems. This upfield shift was less pronounced for the fluorine of the FU7.A66 base-pair, located at the base of the acceptor stem, an indication that FU7 is only partially stacked on the adjacent G49 in the continuous acceptor stem/T-stem helix. An unanticipated finding was that the 19F resonances of 5-fluorouracil residues wobble base-paired with guanine were shifted 4 to 5 p.p.m. downfield of those from fluorouracil residues paired with A. In the 19F NMR spectra of all fluorinated tRNAs studied, the farthest downfield peak corresponded to FU55, which replaced the conserved pseudouridine normally found at this position.
J Mol Biol 1992 Oct 20
PMID:Correlations between fluorine-19 nuclear magnetic resonance chemical shift and the secondary and tertiary structure of 5-fluorouracil-substituted tRNA. 127 81

3'-Fluoro-2',3'-dideoxythymidine 5'-(alpha-methylphosphonyl)-beta, gamma-diphosphate (I) and 2'-deoxythymidine 5'-(alpha-methylphosphonyl)-beta,gamma-diphosphate (II) were synthesised. Reverse transcriptases of HIV and avian myeloblastosis virus, rat liver DNA polymerase beta, calf thymus terminal deoxynucleotidyl transferase and E. coli DNA polymerase I KF incorporated both compounds into the growing DNA chain, KF being the least effective. Compound I revealed termination substrate properties, but II was repeatedly incorporated into the DNA chain, for example, by HIV reverse transcriptase - up to 8 residues. Human placenta DNA polymerases alpha and epsilon incorporated neither I nor II into the DNA chain, although DNA synthesis, catalyzed by all the investigated enzymes, was inhibited in the presence of I or II and compound II was a more effective inhibitor then I. The DNA fragments containing alpha-phosphonomethyl groups were hydrolyzed by 3'----5' exonuclease of DNA polymerase I and not hydrolyzed by ExoIII from E. coli.
Mol Biol (Mosk)
PMID:[Formation of phosphonoester bonds, catalyzed by DNA polymerases]. 172 22

Fluoride is known to cause ectopic calcification. The biochemical mechanism(s) involved in the initiation of calcification is not understood and the accompanying ultrastructural changes remain to be elucidated. Therefore, certain relevant parameters have been investigated in the aorta of rabbits administered fluoride, 10 mg NaF/kg body wt, every 24 hr for 17 and 24 months. The significant findings are: (i) degeneration of smooth muscle fibers in the tunica media of the aorta, (ii) presence of electron-dense granules in the mitochondria and on the inner surface of the plasma membrane of smooth muscle cells, (iii) presence of matrix vesicles with electron-dense deposits, (iv) enhanced calcium content and the Ca/P ratio, and (v) increased total glycosaminoglycan (GAG) content with reduced dermatan sulfate. The presence of electron-dense granules in the mitochondria, on the plasma membrane and matrix vesicles is suggestive of the process of calcification. The enhanced calcium content as well as the Ca/P ratio supports the view that the aorta is undergoing mineralization. The total GAG is enhanced, possibly due to an increase in the content of GAGs other than isomers of chondroitin. The observation that conveys an important message is that the dermatan sulfate normally known to exist in high concentrations in soft tissues begins to decrease as the process of calcification sets in. This perhaps would hold true and may serve as an index in the process of ectopic calcification.
Exp Mol Pathol 1990 Aug
PMID:Aortic calcification in chronic fluoride poisoning: biochemical and electronmicroscopic evidence. 220 10

The peptidyl trifluoromethyl ketones Ac-Phe-CF3 (1) and Ac-Leu-Phe-CF3 (2) are inhibitors of chymotrypsin. They differ in Ki (20 and 2 microM, respectively) as well as in their kinetics of association with chymotrypsin in that 1 is rapidly equilibrating, with an association rate too fast to be observed by steady-state techniques, while 2 is "slow binding", as defined by Morrison and Walsh [Morrison, J. F., & Walsh, C. T. (1988) Adv. Enzymol. Relat. Areas Mol. Biol. 61, 202], with a second-order association rate constant of 750 M-1 s-1 at pH 7.0 [Imperiali, B., & Abeles, R. (1986) Biochemistry 25, 3760]. The crystallographic structures of the complexes of gamma-chymotrypsin with inhibitors 1 and 2 have been determined in order to establish whether structural or conformational differences can be found which account for different kinetic and thermodynamic properties of the two inhibitors. In both complexes, the active-site Ser 195 hydroxyl forms a covalent hemiketal adduct with the trifluoromethyl ketone moiety of the inhibitor. In both complexes, the trifluoromethyl group is partially immobilized, but differences are observed in the degree of interaction of fluorine atoms with the active-site His 57 imidazole ring, with amide nitrogen NH 193, and with other portions of the inhibitor molecule. The enhanced potency of Ac-Leu-Phe-CF3 relative to Ac-Phe-CF3 is accounted for by van der Waals interactions of the leucine side chain of the inhibitor with His 57 and Ile 99 side chains and by a hydrogen bond of the acetyl terminus with amide NH 216 of the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Structure of chymotrypsin-trifluoromethyl ketone inhibitor complexes: comparison of slowly and rapidly equilibrating inhibitors. 227 20

The interaction of lambda cro repressor with DNA is probed using synthetic 17 base-pair OR3 operators in which 5-fluorodeoxyuridine has been systematically incorporated at each of the nine positions normally occupied by a thymidine residue. By monitoring changes in chemical shift of the fluorine resonances upon cro repressor binding in aqueous buffers of varying 2H2O content, we have examined the specific cro repressor-OR3 DNA complex in detail. The results are interpreted in the context of the popular model for cro repressor-OR3 complex derived from the three-dimensional structure of the cro repressor in the absence of DNA. The results presented here not originally predicted by the model are: (1) there is an asymmetry in the environment at the two ends of the operator, although the base-pairs involved and the cro repressor dimer are symmetric; (2) there appears to be distortion of the DNA helix at two distinct positions; (3) changes of the DNA environment in the middle of the helix suggest additional DNA distortion not near the contact areas proposed in the model.
J Mol Biol 1989 Jan 05
PMID:Lambda cro repressor complex with OR3 operator DNA. 19F nuclear magnetic resonance observations. 252 53

We have examined the validity of using fluorine-substituted estrogens as probes to assess the significance of 2- and 4-hydroxylation in estrogen-induced carcinogenesis in the hamster. Liver microsomes from castrated hamsters were incubated with 2-fluoro-, 4-fluoro-, or 2,4-difluoroestradiols and analogous bromo-substituted estradiols to determine the extent of 2- and 4-hydroxylation with these substrates. Estrogen 2- and 4-hydroxylase activity was determined by radioenzymatic assay, and the 3H-labeled monomethyl ether products were identified by high performance liquid chromatography. With unsubstituted 17 beta-estradiol as substrate, 97% of the product formed was 2-hydroxylated, and 3% was 4-hydroxylated. The monosubstituted fluoroestradiols exhibited more than a 2-fold enhanced ability to form catechol estrogens compared with their corresponding bromoestradiols. Data presented herein indicate substantial defluorination when 2-fluoroestradiol was the substrate, which amounted to 36% of the total product formed, and 32% of the rate of 2-hydroxylation found with unsubstituted 17 beta-estradiol as substrate. Interestingly, the rate of 4-hydroxylation was elevated 20- and 6.7-fold, respectively, when 2-fluoroestradiol and 2,4-difluoroestradiol were the substrates compared to the rate with 17 beta-estradiol. Moreover, both 4-fluoroestradiol and 2,4-difluoroestradiol exhibited at least a 1.6-fold greater rate of 2-hydroxylation compared with 17 beta-estradiol. In contrast, the rate of dehalogenation with 2-bromoestradiol was only 12% of that found with 2-fluoroestradiol. No debromination was obtained with 4-bromoestradiol, and essentially no catechols were formed using 2,4-dibromoestradiol as substrate with these hamster liver microsomes. These data clearly provide evidence for defluorination of these substituted estrogens, particularly at the C-2 position, and seriously hamper the use of fluoroestrogens in studies of hormonal carcinogenicity.
Mol Pharmacol 1985 May
PMID:Catechol formation of fluoro- and bromo-substituted estradiols by hamster liver microsomes. Evidence for dehalogenation. 298 51

The relevance of protein phosphorylation, transphosphorylation and binding phenomena in the kinetics of the ATP-induced assembly of cycle-purified microtubule protein from mammalian brain were studied. ATP was able to induce the polymerization of microtubules of normal appearance. However, the assembled structures, were unstable and microtubules depolymerized after achievement of a transitory maximum. Cyclic AMP reduced the amplitude of the polymerization maximum in a concentration-dependent manner, correlating with the stimulation of the endogenous phosphorylation reaction. When microtubule assembly was induced by GTP, in the presence of various concentrations of ATP, the slope of the depolymerization phase was found to depend on the concentration of ATP. Fluoride ion inhibited the endogenous phosphorylation reaction and reduced the disassembly rate, in a concentration-dependent manner. Evidence is also presented indicating that ATP did not bind to phosphocellulose-purified tubulin. These results further contribute to indicate that ATP and cyclic AMP, acting coordinately to control the phosphorylation extent of microtubule proteins are important factors to determine microtubule stability within the cell. Some implications of this mechanism for the regulation by cAMP of the initiation of DNA synthesis and mitosis are considered.
Mol Cell Biochem 1987 Mar
PMID:Effects of ATP and cyclic AMP on the in vitro assembly and stability of mammalian brain microtubules. 303 63


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